A number of herpesviruses are suspected of being oncogenic in humans and animals. Because of the low in vitro transformation rate of these viruses, little information is available concerning molecular events leading to cell transformation. Human cytomegalovirus (CMV), a herpesvirus that is suspected of having oncogenic properties, provides an ideal model in which to examine molecular events involved in transformation and permissiveness in cells. Human CMV produces abnormal changes in cell kinetics in abortive infections, stimulates cell DNA synthesis in permissive and nonpermissive cells, and is capable of in vitro virus transformation following abortive infections. We intend to examine those properties shared by human CMV and known oncogenic DNA viruses and to investigate virus and cell factors controlling permissiveness of CMV in certain cell types. Using rabbit lung fibroblasts as a nonpermissive system in which early functions of CMV are expressed, and human embryo lung fibroblasts as a permissive system, we will examine the effect of CMV on cell kinetics. Quantitative autoradiography, DNA cytophotometry, and mitotic counts will be used to determine the fate of cells stimulated by CMV to enter the S phase of the cell cycle. Parameters to be examined include DNA content distribution of individual cells, length of S, rate of DNA synthesis, and the kinetics of cell DNA synthesis. We intend to use this system to investigate the expression of CMV in abortive infections and the extent of virus expression in cells which undergo cell division following abortive infection. Virus expression will be determined by antigen expression and DNA transcription. Preliminary studies indicate that CMV preferentially infects T lymphoblastoid cells but can persistently infect B lymphoblastoid cells. We intend to use this system to detect the cell or virus factors which may control permissiveness in these cells. An attempt will be made to understand the relationship between cell and virus DNA synthesis by determining the nature of the cell DNA induced by CMV to replicate.